Sexual differentiation of synaptic connectivity and neuronal plasma membrane in the arcuate nucleus of the rat hypothalamus.

Plasma membranes of the hypothalamic arcuate neurons of the rat show a sexually dimorphic phenotype: the numerical density of intramembrane protein particles is greater in females. Male and female Sprague-Dawley rats, 10, 20 and 100 days old, were studied in order to determine whether sexual differentiation of the neuronal plasma membrane in the soma of arcuate neurons is associated with the establishment of sex differences in the pattern of axo-somatic synaptic contacts. Axo-somatic synapses were counted in thin sections of the arcuate nucleus and intramembrane particles were assessed in freeze-fracture replicas of the neuronal membrane. The number of synapses per length of perikaryal membrane increased from day 10 to day 20 in both sexes, reaching by 20 days values similar to those found on day 100. A sex difference in the number of synapses was observed only in 20-day-old and 100-day-old rats: neurons from females showed a greater number of presynaptic inputs than males (P less than 0.05). This sex difference was abolished by administration of testosterone propionate to 5-day-old females. Quantitative evaluation of freeze-fracture replicas of the arcuate neuronal perikarya revealed sex differences in the numerical density of intramembrane particles at all time points studied: neurons from females contained significantly more particles in their plasma membranes than neurons from males or androgenized females of the same age (P less than 0.001). These results indicate that sexual differentiation of the plasma membrane in neuronal somas precedes the establishment of sex differences in axo-somatic synapses. The results are compatible with a possible role of neuronal membranes in the sexual differentiation of synaptic connectivity.